[4] These data suggest that CLDN-1 and OCLN expression may be significantly influenced at post-transcriptional level in the presence of HCV. Dysregulated microRNA expression patterns have been reported in many human diseases, such as various types of cancers, as well as metabolic, infectious, chronic inflammatory, and autoimmune diseases.[24, 25] Regarding HCV infection, the liver-specific miR-122 has been reported to enhance HCV replication in human hepatoma cells by binding to the 5′ UTR of HCV, and sequestration of miR-122 by antisense oligonucleotide

decreased HCV replication and translation in vitro[16, 23, 26-28] and in vivo.[29, 30] However, no[31] or only weak positive correlation[13] could be found between hepatic miR-122 and serum HCV see more load, while no correlation could be observed between hepatic miR-122 and hepatic HCV load.[13, 31] Further, miR-122 was downregulated in acute HCV infection in human hepatoma cells at Bafilomycin A1 in vivo day 4 post-infection,[9] and IFN-β reduced

the expression of miR-122.[17] This indicates that miR-122 may be affected by the consequences of HCV infection and IFN treatment. In the present study, higher expression level of miR-122 was associated with higher viral load in patient sera; however, no significant difference was found in hepatic miR-122 expression at the time of HCV recurrence compared with normal liver tissue. Applying the same comparison, the expression levels of miR-21 and miR-194 were decreased, whereas those of miR-99a* and miR-224 were increased upon HCV reactivation when compared with the normal hepatic expression of these miRs. miR-21 and miR-194 were found to influence CLDN-1 mRNA expression, while miR-99a* might control SCARB-1 expression and miR-224 might modulate mRNA of OCLN. In silico sequence comparison also suggests the binding of miR-194 to mRNAs of OCLN and CD81. Therefore, the observed expressional increase of CLDN-1 and OCLN[4, 5] might be caused by the decrease of miR-194 and miR-21 expressions upon HCV infection. This would represent in vivo

function of these miRs in the post-transcriptional regulation RANTES of HCV receptors. The high expression of miR-194 in normal liver tissue has been known for a long time.[32] miR-194 plays a role in the regulation of hepatic stellate cell activation during fibrogenesis[33] and suppresses N-cadherin expression, leading to inhibition of cell migration, adhesion, and metastasis of hepatocellular carcinoma (HCC) cells.[32] miR-21 has been previously identified as an “onco-miR” because of its abberant expression in multiple malignancies including breast cancer, colon, and HCCs.[34] Interestingly, our dataset showed decreased HCV recurrence-associated expression of miR-21. Certain other changes, however, such as elevated miR-224 expression found in our study during HCV recurrence, were also detected in HCCs induced by HCV infection.